A key role for the c-myc oncogene in cellular proliferation has long been postulated. C-myc may act by modulating the expression of other cellular genes whose products directly control proliferation. Permanent cell lines (in which the endogenous c- mYc gene is tightly regulated by growth factors and cell/cell contact) have been constructed in which expression of an exogenously transfected c-myc gene is controlled by the Drosophila heat shock 70 promoter. Transcription and subsequent translation of the exogenous c-myc gene is specifically induced by mild heat shock. The endogenous c-myc gene is not expressed under these conditions. Compared to heat-shocked cell lines which contain constructs lacking c-myc, several changes in cellular gene expression are observed: (1) two-dimensional analysis of the proteins from c-myc-containing cell lines shows the induction of eight protein species and the repression of five protein species relative to cell lines lacking c-myc; (2) the transcripts of two genes (3CH77 and 3CH92) previously identified as serum inducible are induced when c-myc is expressed; (3) the endogenous heat shock 70 gene may be specifically induced in response to c-myc. Therefore, c-myc expression alters the expression of other cellular genes, including the induction of some known to be expressed only in proliferating cells.